Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2025-09-13 DOI:10.1080/14622416.2025.2558498

Priyanga Ranasinghe, Charindie Peiris, Hajanthy Jeyapragasam, Nirmala D Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake

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引用次数: 0

Abstract

Background: Ensuring the efficacy and safety of medicines acting on the central nervous system (CNS) remains a challenge due to their complex pharmacokinetics and inter-individual variability in response. We describe the frequencies of pharmacogenomic variants affecting CNS drug metabolism in a Sri Lankan population.

Methods: Pharmacogenomic data pertaining to genes of interest were obtained from the Pharmacogenomics Knowledgebase database. Pharmacokinetically relevant cytochrome P450 isoforms were selected. Their frequencies in Sri Lankans were obtained from an anonymized database derived from 690 participants, from the Human Genetics Unit, Faculty of Medicine, University of Colombo. Minor allele frequencies (MAFs) of these variants were calculated and compared with other populations.

Results: MAFs of CYP2C19 rs4244285, CYP2D6 rs16947, CYP2D6 rs1058164, CYP2D6 rs1135840, and CYP2B6 rs3745274 were notably high at 40.9% (95%CI:38.3-43.5), 58.0% (95%CI:55.3-60.6), 43.8% (95%CI:41.1-46.4), 44.1% (95%CI:41.5-46.8), and 39.8% (95%CI:37.2-42.4), respectively. MAFs of CYP2C9 rs72558189, CYP2C19 rs4244285, CYP2D6 rs77913725, CYP2D6 rs1135828, and CYP2B6 rs3745274 recorded the highest in Sri Lankans when compared to all other populations. A lower prevalence was noted in MAFs of CYP2D6 rs1065852, CYP2D6 rs16947, and CYP2D6 rs28371706.

Conclusion: Sri Lankans exhibit an increased susceptibility to adverse reactions with common antidepressants, antipsychotics, and analgesics and reduced efficacy to opioid analgesics. These findings highlight the need for population-specific pharmacogenomic guidelines.

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影响斯里兰卡人中枢神经系统药物疗效和安全性的药物基因组变异。

背景：由于药物作用于中枢神经系统（CNS）的药代动力学复杂且个体间反应差异，确保药物的有效性和安全性仍然是一个挑战。我们描述了斯里兰卡人群中影响中枢神经系统药物代谢的药物基因组变异的频率。方法：从药物基因组学知识库数据库中获取相关基因的药物基因组学数据。选择与药代动力学相关的细胞色素P450亚型。他们在斯里兰卡人中的频率是从来自科伦坡大学医学院人类遗传学部门的690名参与者的匿名数据库中获得的。计算这些变异的次要等位基因频率（MAFs），并与其他群体进行比较。结果：CYP2C19 rs4244285、CYP2D6 rs16947、CYP2D6 rs1058164、CYP2D6 rs1135840、CYP2B6 rs3745274的maf均较高，分别为40.9% （95%CI:38.3 ~ 43.5）、58.0% （95%CI:55.3 ~ 60.6）、43.8% （95%CI:41.1 ~ 46.4）、44.1% （95%CI:41.5 ~ 46.8）、39.8% （95%CI:37.2 ~ 42.4）。与所有其他人群相比，斯里兰卡人CYP2C9 rs72558189、CYP2C19 rs4244285、CYP2D6 rs77913725、CYP2D6 rs1135828和CYP2B6 rs3745274的maf最高。CYP2D6 rs1065852、CYP2D6 rs16947和CYP2D6 rs28371706的maf患病率较低。结论：斯里兰卡人对常见抗抑郁药、抗精神病药和镇痛药的不良反应的易感性增加，对阿片类镇痛药的疗效降低。这些发现强调了制定针对特定人群的药物基因组学指南的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.